Objective: Our previous research on the in vitro interaction of carcinogens with transforming DNA has demonstrated conclusively that ultimate carcinogens (active forms) are mutagenic. Recent physicochemical and genetic evidence shows that repair enzymes can recognize carcinogen- induced lesions in DNA. Evidence of species differences in the action of carcinogens suggests that they be tested in human cells. The present study makes use of normal, diploid human cells in culture to detect the interaction of selected representatives of the following classes of carcinogens: a) polycyclic aromatic hydrocarbons; b) aromatic amides and amines; c) alkylating agents; d) other electrophilic reactants. Approach: We compare the cytotoxic effect of such compounds on normal, diploid human cells and determine whether they interact with DNA to produce mutations. 8-azaguanine resistance serves as the selection system. The induced mutants are characterized as to their level of hypoxanthine-quanine-phosphoribosyl transferase activity and the heritability of the phenotype in the absence of mutagen or selective agent. Using several physicochemical techniques, we determine if cellular enzymatic repair of lesions in DNA induced by such carcinogens occurs and compare the types of lesions induced by each class to see if the human cells repair such damage. Finally, we will develop strains of diploid human cells which differ in their capacity to repair lesions in DNA, to determine the effect of repair processes on the cytotoxic and mutagenic action of the carcinogens.